Progress on this multi-institutional collaborative project has focused primarily on quantitative morphometric analysis in the brains of behaviorally characterized subjects in relation to estrogen status. In a recently published study, for example, Hara and colleagues tested whether mitochondria morphology and number are altered in the prefrontal cortex during aging in rhesus monkeys. Notably, estrogen treatment reversed both the behavioral deficits and aged-related changes in mitochondria shape observed in ovariectomized females. These findings are consistent with the idea that hormone replacement benefits the cognitive outcome of aging partly through influencing mitochondrial function, with downstream effects on synaptic integrity. The results complement other recently published evidence from this model demonstrating that, in contrast to the behavioral and synaptic effects of cyclic estrogen treatment we reported earlier, multiple hormone therapy regimens adapted from clinical practice in women fail to improve cognitive function or dendritic spine density in the prefrontal cortex. Overall this project continues to clarify a number of significant issues concerning the modulatory influence of ovarian hormones on normal cognitive aging.